Structural Insight into Evolution of the Quinone Binding Site in Complex II

The Complex II family encompasses membrane bound succinate:quinones reductases and quinol:fumarate reductases that catalyze interconversion of succinate and fumarate coupled with reduction and oxidation of quinone. These enzymes are found in all biological genres and share a modular structure where a highly conserved soluble domain is bound to a membrane-spanning domain that is represented by distinct variations. The current classification of the complex II family members is based on the number of subunits and co-factors in the membrane anchor (types A-F). This classification also provides insights into possible evolutionary paths and suggests that some of the complex II enzymes (types A-C) co-evolved as the whole assembly. Origin of complex II types D and F may have arisen from independent events of de novo association of the conserved soluble domain with a new anchor. Here we analyze a recent structure of Mycobacterium smegmatis Sdh2, a complex II enzyme with two transmembrane subunits and two heme b molecules. This analysis supports an earlier hypothesis suggesting that mitochondrial complex II (type C) with a single heme b may have evolved as an assembled unit from an ancestor similar to M. smegmatis Sdh2.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic €32.70 /Month

Buy Now

Price includes VAT (France)

Instant access to the full article PDF.

Rent this article via DeepDyve

Similar content being viewed by others

Cryo-EM structure of trimeric Mycobacterium smegmatis succinate dehydrogenase with a membrane-anchor SdhF

Article Open access 25 August 2020

Rieske/Cytochrome b Complexes: The Turbo Chargers of Chemiosmosis

Chapter © 2014

Structure of a functional obligate complex III2IV2 respiratory supercomplex from Mycobacterium smegmatis

Article 05 December 2018

Abbreviations

distal heme b

proximal heme b

distal quinone binding site

proximal quinone binding site

References

  1. Cecchini, G. (2003) Function and structure of complex II of the respiratory chain, Annu. Rev. Biochem., 72, 77-109, https://doi.org/10.1146/annurev.biochem.72.121801.161700. ArticleCASPubMedGoogle Scholar
  2. Hagerhall, C. (1997) Succinate: quinone oxidoreductases. Variations on a conserved theme, Biochim. Biophys. Acta, 1320, 107-141, https://doi.org/10.1016/s0005-2728(97)00019-4. ArticleCASPubMedGoogle Scholar
  3. Sharma, P., Maklashina, E., Cecchini, G., and Iverson, T. M. (2019) Maturation of the respiratory complex II flavoprotein, Curr. Opin. Struct. Biol., 59, 38-46, https://doi.org/10.1016/j.sbi.2019.01.027. ArticleCASPubMedPubMed CentralGoogle Scholar
  4. Sharma, P., Maklashina, E., Cecchini, G., and Iverson, T. M. (2018) Crystal structure of an assembly intermediate of respiratory Complex II, Nat. Commun., 9, 274, https://doi.org/10.1038/s41467-017-02713-8. ArticleCASPubMedPubMed CentralGoogle Scholar
  5. Kounosu, A. (2014) Analysis of covalent flavinylation using thermostable succinate dehydrogenase from Thermus thermophilus and Sulfolobus tokodaii lacking SdhE homologs, FEBS Lett., 588, 1058-1063, https://doi.org/10.1016/j.febslet.2014.02.022. ArticleCASPubMedGoogle Scholar
  6. Lill, R., and Freibert, S. A. (2020) Mechanisms of mitochondrial iron-sulfur protein biogenesis, Annu. Rev. Biochem., 89, 471-499, https://doi.org/10.1146/annurev-biochem-013118-111540. ArticleCASPubMedGoogle Scholar
  7. Bai, Y., Chen, T., Happe, T., Lu, Y., and Sawyer, A. (2018) Iron-sulphur cluster biogenesis via the SUF pathway, Metallomics, 10, 1038-1052, https://doi.org/10.1039/c8mt00150b. ArticlePubMedGoogle Scholar
  8. Heuts, D. P., Scrutton, N. S., McIntire, W. S., and Fraaije, M. W. (2009) What’s in a covalent bond? On the role and formation of covalently bound flavin cofactors, FEBS J., 276, 3405-3427, https://doi.org/10.1111/j.1742-4658.2009.07053.x. ArticleCASPubMedGoogle Scholar
  9. Hao, H. X., Khalimonchuk, O., Schraders, M., Dephoure, N., Bayley, J. P., et al. (2009) SDH5, a gene required for flavination of succinate dehydrogenase, is mutated in paraganglioma, Science, 325, 1139-1142, https://doi.org/10.1126/science.1175689. ArticleCASPubMedGoogle Scholar
  10. McNeil, M. B., Clulow, J. S., Wilf, N. M., Salmond, G. P., and Fineran, P. C. (2012) SdhE is a conserved protein required for flavinylation of succinate dehydrogenase in bacteria, J. Biol. Chem., 287, 18418-18428, https://doi.org/10.1074/jbc.M111.293803. ArticleCASPubMedPubMed CentralGoogle Scholar
  11. Van Vranken, J. G., Na, U., Winge, D. R., and Rutter, J. (2015) Protein-mediated assembly of succinate dehydrogenase and its cofactors, Crit. Rev. Biochem. Mol. Biol., 50, 168-180, https://doi.org/10.3109/10409238.2014.990556. ArticleCASPubMedGoogle Scholar
  12. Moosavi, B., Berry, E. A., Zhu, X. L., Yang, W. C., and Yang, G. F. (2019) The assembly of succinate dehydrogenase: a key enzyme in bioenergetics, Cell. Mol. Life Sci., 76, 4023-4042, https://doi.org/10.1007/s00018-019-03200-7. ArticleCASPubMedGoogle Scholar
  13. Tedeschi, G., Negri, A., Mortarino, M., Ceciliani, F., Simonic, T., et al. (1996) L-aspartate oxidase from Escherichia coli. II. Interaction with C4 dicarboxylic acids and identification of a novel L-aspartate: fumarate oxidoreductase activity, Eur. J. Biochem., 239, 427-433, https://doi.org/10.1111/j.1432-1033.1996.0427u.x. ArticleCASPubMedGoogle Scholar
  14. Taylor, P., Pealing, S. L., Reid, G. A., Chapman, S. K., and Walkinshaw, M. D. (1999) Structural and mechanistic mapping of a unique fumarate reductase, Nat. Struct. Biol., 6, 1108-1112, https://doi.org/10.1038/70045. ArticleCASPubMedGoogle Scholar
  15. Maklashina, E., Rajagukguk, S., Iverson, T. M., and Cecchini, G. (2018) The unassembled flavoprotein subunits of human and bacterial complex II have impaired catalytic activity and generate only minor amounts of ROS, J. Biol. Chem., 293, 7754-7765, https://doi.org/10.1074/jbc.RA118.001977. ArticleCASPubMedPubMed CentralGoogle Scholar
  16. Maklashina, E., Iverson, T. M., Sher, Y., Kotlyar, V., Andrell, J., et al. (2006) Fumarate reductase and succinate oxidase activity of Escherichia coli complex II homologs are perturbed differently by mutation of the flavin binding domain, J. Biol. Chem., 281, 11357-11365, https://doi.org/10.1074/jbc.M512544200. ArticleCASPubMedGoogle Scholar
  17. Hägerhäll, C., and Hederstedt, L. (1996) A structural model for the membrane-integral domain of succinate: quinone oxidoreductases, FEBS Lett., 389, 25-31, https://doi.org/10.1016/0014-5793(96)00529-7. ArticlePubMedGoogle Scholar
  18. Lancaster, C. R. (2013) The di-heme family of respiratory complex II enzymes, Biochim. Biophys. Acta, 1827, 679-687, https://doi.org/10.1016/j.bbabio.2013.02.012. ArticleCASPubMedGoogle Scholar
  19. Iverson, T. M., Luna-Chavez, C., Cecchini, G., and Rees, D. C. (1999) Structure of the Escherichia coli fumarate reductase respiratory complex, Science, 284, 1961-1966, https://doi.org/10.1126/science.284.5422.1961. ArticleCASPubMedGoogle Scholar
  20. Yankovskaya, V., Horsefield, R., Tornroth, S., Luna-Chavez, C., Miyoshi, H., et al. (2003) Architecture of succinate dehydrogenase and reactive oxygen species generation, Science, 299, 700-704, https://doi.org/10.1126/science.1079605. ArticleCASPubMedGoogle Scholar
  21. Huang, L. S., Shen, J. T., Wang, A. C., and Berry, E. A. (2006) Crystallographic studies of the binding of ligands to the dicarboxylate site of Complex II, and the identity of the ligand in the “oxaloacetate-inhibited” state, Biochim. Biophys. Acta, 1757, 1073-1083, https://doi.org/10.1016/j.bbabio.2006.06.015. ArticleCASPubMedPubMed CentralGoogle Scholar
  22. Sun, F., Huo, X., Zhai, Y., Wang, A., Xu, J., et al. (2005) Crystal structure of mitochondrial respiratory membrane protein complex II, Cell, 121, 1043-1057, https://doi.org/10.1016/j.cell.2005.05.025. ArticleCASPubMedGoogle Scholar
  23. Inaoka, D. K., Shiba, T., Sato, D., Balogun, E. O., Sasaki, T., et al. (2015) Structural insights into the molecular design of flutolanil derivatives targeted for fumarate respiration of parasite mitochondria, Int. J. Mol. Sci., 16, 15287-15308, https://doi.org/10.3390/ijms160715287. ArticleCASPubMedPubMed CentralGoogle Scholar
  24. Hards, K., Rodriguez, S. M., Cairns, C., and Cook, G. M. (2019) Alternate quinone coupling in a new class of succinate dehydrogenase may potentiate mycobacterial respiratory control, FEBS Lett., 593, 475-486, https://doi.org/10.1002/1873-3468.13330. ArticleCASPubMedGoogle Scholar
  25. Zhou, X., Gao, Y., Wang, W., Yang, X., Yang, X., et al. (2021) Architecture of the mycobacterial succinate dehydrogenase with a membrane-embedded Rieske FeS cluster, Proc. Natl. Acad. Sci. USA, 118, e2022308118, https://doi.org/10.1073/pnas.2022308118. ArticleCASPubMedPubMed CentralGoogle Scholar
  26. Lancaster, C. R., Kroger, A., Auer, M., and Michel, H. (1999) Structure of fumarate reductase from Wolinella succinogenes at 2.2 Å resolution, Nature, 402, 377-385, https://doi.org/10.1038/46483. ArticleCASPubMedGoogle Scholar
  27. Guan, H. H., Hsieh, Y. C., Lin, P. J., Huang, Y. C., Yoshimura, M., et al. (2018) Structural insights into the electron/proton transfer pathways in the quinol:fumarate reductase from Desulfovibrio gigas, Sci. Rep., 8, 14935, https://doi.org/10.1038/s41598-018-33193-5. ArticleCASPubMedPubMed CentralGoogle Scholar
  28. Gong, H., Gao, Y., Zhou, X., Xiao, Y., Wang, W., et al. (2020) Cryo-EM structure of trimeric Mycobacterium smegmatis succinate dehydrogenase with a membrane-anchor SdhF, Nat. Commun., 11, 4245, https://doi.org/10.1038/s41467-020-18011-9. ArticleCASPubMedPubMed CentralGoogle Scholar
  29. Juhnke, H. D., Hiltscher, H., Nasiri, H. R., Schwalbe, H., and Lancaster, C. R. (2009) Production, characterization and determination of the real catalytic properties of the putative “succinate dehydrogenase” from Wolinella succinogenes, Mol. Microbiol., 71, 1088-1101, https://doi.org/10.1111/j.1365-2958.2008.06581.x. ArticleCASPubMedPubMed CentralGoogle Scholar
  30. Tran, Q. M., Rothery, R. A., Maklashina, E., Cecchini, G., and Weiner, J. H. (2007) Escherichia coli succinate dehydrogenase variant lacking the heme b, Proc. Natl. Acad. Sci. USA, 104, 18007-18012, https://doi.org/10.1073/pnas.0707732104. ArticlePubMedPubMed CentralGoogle Scholar
  31. Maklashina, E., Hellwig, P., Rothery, R. A., Kotlyar, V., Sher, Y., et al. (2006) Differences in protonation of ubiquinone and menaquinone in fumarate reductase from Escherichia coli, J. Biol. Chem., 281, 26655-26664, https://doi.org/10.1074/jbc.M602938200. ArticlePubMedGoogle Scholar
  32. Schirawski, J., and Unden, G. (1998) Menaquinone-dependent succinate dehydrogenase of bacteria catalyzes reversed electron transport driven by the proton potential, Eur. J. Biochem, 257, 210-215, https://doi.org/10.1046/j.1432-1327.1998.2570210.x. ArticleCASPubMedGoogle Scholar
  33. Madej, M. G., Nasiri, H. R., Hilgendorff, N. S., Schwalbe, H., Unden, G., et al. (2006) Experimental evidence for proton motive force-dependent catalysis by the diheme-containing succinate:menaquinone oxidoreductase from the Gram-positive bacterium Bacillus licheniformis, Biochemistry, 45, 15049-15055, https://doi.org/10.1021/bi0618161. ArticleCASPubMedGoogle Scholar
  34. Madej, M. G., Nasiri, H. R., Hilgendorff, N. S., Schwalbe, H., and Lancaster, C. R. (2006) Evidence for transmembrane proton transfer in a dihaem-containing membrane protein complex, EMBO J., 25, 4963-4970, https://doi.org/10.1038/sj.emboj.7601361. ArticleCASPubMedPubMed CentralGoogle Scholar
  35. Schafer, G., Anemuller, S., and Moll, R. (2002) Archaeal complex II: “classical” and “non-classical” succinate:quinone reductases with unusual features, Biochim. Biophys. Acta, 1553, 57-73, https://doi.org/10.1016/s0005-2728(01)00232-8. ArticleCASPubMedGoogle Scholar
  36. Maklashina, E., Rajagukguk, S., McIntire, W. S., and Cecchini, G. (2010) Mutation of the heme axial ligand of Escherichia coli succinate-quinone reductase: implications for heme ligation in mitochondrial complex II from yeast, Biochim. Biophys. Acta, 1797, 747-754, https://doi.org/10.1016/j.bbabio.2010.01.019. ArticleCASPubMedPubMed CentralGoogle Scholar
  37. Lancaster, C. R., Gorss, R., Haas, A., Ritter, M., Mantele, W., et al. (2000) Essential role of Glu-C66 for menaquinol oxidation indicates transmembrane electrochemical potential generation by Wolinella succinogenes fumarate reductase, Proc. Natl. Acad. Sci. USA, 97, 13051-13056, https://doi.org/10.1073/pnas.220425797. ArticleCASPubMedPubMed CentralGoogle Scholar
  38. Maklashina, E., and Cecchini, G. (2010) The quinone-binding and catalytic site of complex II, Biochim. Biophys. Acta, 1797, 1877-1882, https://doi.org/10.1016/j.bbabio.2010.02.015. ArticleCASPubMedPubMed CentralGoogle Scholar
  39. Silkin, Y., Oyedotun, K. S., and Lemire, B. D. (2007) The role of Sdh4p Tyr-89 in ubiquinone reduction by the Saccharomyces cerevisiae succinate dehydrogenase, Biochim. Biophys. Acta, 1767, 143-150, https://doi.org/10.1016/j.bbabio.2006.11.017. ArticleCASPubMedGoogle Scholar
  40. Tran, Q. M., Rothery, R. A., Maklashina, E., Cecchini, G., and Weiner, J. H. (2006) The quinone binding site in Escherichia coli succinate dehydrogenase is required for electron transfer to the heme b, J. Biol. Chem., 281, 32310-32317, https://doi.org/10.1074/jbc.M607476200. ArticleCASPubMedGoogle Scholar
  41. Tran, Q. M., Fong, C., Rothery, R. A., Maklashina, E., Cecchini, G., and Weiner, J. H. (2012) Out of plane distortions of the heme b of Escherichia coli succinate dehydrogenase, PLoS One, 7, e32641, https://doi.org/10.1371/journal.pone.0032641. ArticleCASPubMedPubMed CentralGoogle Scholar
  42. Maklashina, E., Rothery, R. A., Weiner, J. H., and Cecchini, G. (2001) Retention of heme in axial ligand mutants of succinate-ubiquinone oxidoreductase (complex II) from Escherichia coli, J. Biol. Chem., 276, 18968-18976, https://doi.org/10.1074/jbc.M011270200. ArticleCASPubMedGoogle Scholar
  43. Gu, L. Q., Yu, L., and Yu, C. A. (1990) Effect of substituents of the benzoquinone ring on electron-transfer activities of ubiquinone derivatives, Biochim. Biophys. Acta, 1015, 482-492, https://doi.org/10.1016/0005-2728(90)90082-f. ArticleCASPubMedGoogle Scholar

Acknowledgments

I dedicate this review to my mentor Andrei Vinogradov. He devoted a large portion of his scientific life to study mitochondrial complex II, which he often called “my first love in science”. I also wish to thank Gary Cecchini for reading the manuscript.

Author information

Authors and Affiliations

  1. Department of Biochemistry and Biophysics, University of California, San Francisco, 94143, San Francisco, CA, USA Elena Maklashina
  1. Elena Maklashina